Molecular Pathology of Prions

Abstract

Edited by Harry F. Baker, Humana PressMolecular Pathology of Prions is multiauthored text that describes the recent advances in the molecular biology of prion disorders. The major goal of the book is to address the pathologic mechanisms leading to the generation of spongiform encephalopathies. This is a timely topic, not only for the fact that Stanley Prusiner and Carleton Gajdusek recently won the Nobel Prize for their work on prions, but also because of the emergence of the new variant of Creutzfeldt-Jakob disease as a result of bovine spongiform encephalopathy in Great Britain. Although the book is part of a Methods in Molecular Medicine series, the editor has specifically not used the cookbook method format that was used in a previous edition in 1996. Instead, the editor has assembled a cross-section of work by some of the leading researchers in the field and, to use his own words, “I have concentrated on the molecular pathogenesis of prion disease and the emphasis is on the role of the prion protein. There is no mention of the epidemiology of animal and human prion diseases that figured so prominently in the earlier book.” Therefore, the major purpose is to have the authors discuss how their research is addressing some of the unanswered questions regarding the biology of the prion protein.The book has 14 chapters, which are preceded by a well-done philosophical overview by Rosalind M. Ridley about how novel hypotheses, of which the prion hypothesis certainly was one, evolve into scientific fact. The next 2 chapters, by Kretzschmar et al and David R. Brown and Ian M. Jones, respectively, discuss proposed functions of the normal prion protein. Chapter 4, by David R. Brown, describes immunohistochemical analysis of the abnormal prion proteins in bovine spongiform encephalopathy and scrapie. Chapter 6, by Stephen J. DeArmond, gives a very interesting discussion about the differential targeting of neurons by different prion strains. The next chapter, by Glenn C. Telling, describes transgenic animal studies of prion diseases. In this chapter, he details research showing that knock-out animals for the normal prion protein are not able to develop spongiform encephalopathies when inoculated. This finding supports the prion-only hypothesis of prion replication. Chapter 8, by Glatzel et al, is entitled “Prions: From Neurografts to Neuroinvasion.” Chapter 9, by Harris et al, describes work on familial prion diseases in transgenic animals. Chapter 10, by Samar Betmouni and V. Hugh Perry, discusses the role of inflammation in the pathogenesis of prion disease. This had been a previously understudied area, and the authors give a very lucid account of how prion amyloid deposition may in fact be an inflammatory response. In the next chapter, J. Richard Green describes experiments on the electrophysiologic effects of abnormal prions in neuronal cells. Chapter 12, by Martin Jeffery and Jan R. Fraser, presents evidence that there is extracellular conversion of the prion proteins that is typical of classic amyloidosis. The next chapter, by Wisniewski et al, is a very interesting discussion of their work aimed at developing therapeutic agents composed of conformational isoforms of both prions and amyloid-β to block amyloid deposition not only in spongiform encephalopathies, but also in Alzheimer disease. Finally, the last, very provocative chapter, by Wicker et al, describes how prions in yeast may be proteins that mediate inheritance.Overall, the editor has put together work by some of the leading prion researchers that helps clarify the more recent advances in the field. This book would most likely appeal to someone who has a basic working knowledge of prion diseases. Therefore, it would be an excellent addition to the libraries of neuropathologists, neurologists, or molecular neuroscientists. However, it would also be a good resource for and give valuable insights to any of those individuals who are studying the molecular mechanisms of amyloidosis in general.